8KD8

N(5)-hydroxyornithine:cis-anhydromevalonyl coenzyme A-N(5)-transacylase sidF N-terminal domain

8KD8 の概要

• エントリーDOI: 10.2210/pdb8kd8/pdb
• 分子名称: N(5)-hydroxyornithine:cis-anhydromevalonyl coenzyme A-N(5)-transacylase sidF (2 entities in total)
• 機能のキーワード: gnat, sidf, aspergillus fumigatus, siderophore, acetyltransferase, transferase
• 由来する生物種: Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22325.97

構造登録者

Poonsiri, T.,Demitri, N.,Benini, S. (登録日: 2023-08-09, 公開日: 2024-08-14, 最終更新日: 2025-09-03)

主引用文献

Poonsiri, T.,Stransky, J.,Demitri, N.,Haas, H.,Cianci, M.,Benini, S.
SidF, a dual substrate N5-acetyl-N5-hydroxy-L-ornithine transacetylase involved in Aspergillus fumigatus siderophore biosynthesis.
J Struct Biol X, 11:100119-100119, 2025

PubMed Abstract: Siderophore-mediated iron acquisition is essential for the virulence of , a fungus causing life-threatening aspergillosis. Drugs targeting the siderophore biosynthetic pathway could help improve disease management. The transacetylases SidF and SidL generate intermediates for different siderophores in . has a yet unidentified transacetylase that complements SidL during iron deficiency in SidL-lacking mutants. We present the first X-ray structure of SidF, revealing a two-domain architecture with tetrameric assembly. The N-terminal domain contributes to protein solubility and oligomerization, while the C-terminal domain containing the GCN5-related N-acetyltransferase (GNAT) motif is crucial for the enzymatic activity and mediates oligomer formation. Notably, AlphaFold modelling demonstrates structural similarity between SidF and SidL. Enzymatic assays showed that SidF can utilize acetyl-CoA as a donor, previously thought to be a substrate of SidL but not SidF, and selectively uses N5-hydroxy-L-ornithine as an acceptor. This study elucidates the structure of SidF and reveals its role in siderophore biosynthesis. We propose SidF as the unknown transacetylase complementing SidL activity, highlighting its central role in siderophore biosynthesis. Investigation of this uncharacterized GNAT protein enhances our understanding of fungal virulence and holds promise for its potential application in developing antifungal therapies.

PubMed: 39845173
DOI: 10.1016/j.yjsbx.2024.100119

実験手法

X-RAY DIFFRACTION (2.581 Å)